8-Hydroxyquinoline → HCID 66873656, compound

HRID 474951Notes

Reaction equation

HRID 474951 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[N:10]=2)=[CH:5][CH:4]=1.Br[C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29][C:24]=3[N:25]([CH3:28])[C:26]=2[CH:27]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[CH3:28][N:25]1[C:26]2[CH:27]=[C:19]([N:12]3[CH:13]=[CH:14][C:9]([C:6]4[CH:7]=[N:8][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:4][CH:5]=4)=[N:10][C:11]3=[O:15])[CH:20]=[CH:21][C:22]=2[C:23]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29][C:24]1=2

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 58093439tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylateHCID 178517475HCID 178517475, compound

Product 1

HCID 66873656HCID 66873656, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
135 °C

Procedure

A suspension of 4-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-2(1H)-one (69 mg, 0.29 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (120 mg, 0.32 mmol), 8-hydroxyquinoline (8.4 mg, 0.058 mmol) and Cs2CO3 (110 mg, 0.35 mmol) in DMSO (5.0 mL) was degassed under reduced pressure for 30 min. CuI (66.7 mg, 0.35 mmol) was then added to the above solution, and the reaction mixture was degassed under reduced pressure for 5 min. The suspension was then stirred at 135° C. under nitrogen overnight. The suspension was cooled and diluted with ethyl acetate. The resulting mixture was washed with aqueous LiCl (5%), ammonium hydroxide (2×), and brine. The organic extract was separated, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude material was purified by preparative TLC (hexanes/ethyl acetate 1:1 then DCM/MeOH 96:4). The desired band was collected and extracted with dichloromethane. The resulting solution was treated with charcoal, filtered through a pad of celite, and concentrated under reduced pressure to give the title compound (36 mg, 20%) as a yellow foam: 1H NMR (500 MHz, CDCl3) δ 9.36 (s, 1H), 8.76 (d, J=7.0 Hz, 1H), 8.99 (d, J=6.5 Hz, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.58-7.56 (m, 1H), 7.38-7.37 (m, 1H), 7.09-7.08 (m, 1H), 6.93 (d, J=7.0 Hz, 1H), 3.80-3.68 (m, 4H), 3.68 (s, 3H), 3.09-2.99 (m, 4H), 1.49 (s, 9H).

Workup

  1. customwas degassed under reduced pressure for 30 min
  2. customthe reaction mixture was degassed under reduced pressure for 5 min
  3. temperatureThe suspension was cooled
  4. additiondiluted with ethyl acetate
  5. washThe resulting mixture was washed with aqueous LiCl (5%), ammonium hydroxide (2×), and brine
  6. extractionThe organic extract
  7. customwas separated
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting crude material was purified by preparative TLC (hexanes/ethyl acetate 1:1
  11. customThe desired band was collected
  12. extractionextracted with dichloromethane
  13. additionThe resulting solution was treated with charcoal
  14. filtrationfiltered through a pad of celite
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b94b2f2f933843e08a55a4ee144f49b3
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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